Study designed to evaluate the safety and efficacy of AMG 145 compared with Ezetimibe treatment, in people with high cholesterol who have experienced side effects whilst taking existing statin treatment

Phase 1

• Conditions: Hypercholesterolemia; MedDRA version: 19.0Level: LLTClassification code 10020604Term: HypercholesterolemiaSystem Organ Class: 100000004861; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2013-000935-29-NL
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-10
• Last Update Posted: 8 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

1) Subject who has provided informed consent/assent prior to initiation of any study-specific activities/procedures.
2) Male or female = 18 to = 80 years of age at signing of informed consent
3) Subject who is not at LDL-C goal as evidenced by their NCEP ATP III risk category and the following LDL-C levels by central laboratory at screening:
a) Fasting LDL-C = 100 mg/dL (2.59 mmol/L) for subjects with diagnosed CHD or are CHD risk equivalent or
b) Fasting LDL-C = 130 mg/dL (3.37 mmol/L) for subjects without diagnosed CHD or risk equivalent and 2 or more risk factors or
c) Fasting LDL-C = 160 mg/dL (4.14 mmol/L) for subjects without diagnosed CHD or risk equivalent and with 1 or more risk factors or
d) Fasting LDL-C = 190 mg/dL (4.9 mmol/L) for subjects without diagnosed CHD or risk equivalent and with no risk factors
4) Subject who has a history of statin intolerance as evidenced by the following:
a) Unable to tolerate atorvastatin at an average daily dose of 10 mg AND unable to tolerate any other statin at any dose due to skeletal muscle related symptoms (e.g., pain, aches, weakness or cramping)
OR
b) Unable to tolerate at least three statins: one statin at the lowest starting average daily dose (defined below) AND any other two statins at any dose, due to skeletal muscle related symptoms (e.g., pain, aches, weakness or cramping)
- atorvastatin - 5 mg
- simvastatin - 10 mg
- pravastatin - 40 mg
- lovastatin - 20 mg
- fluvastatin - 40 mg
- pitavastatin - 2 mg
OR
c) A documented history of CK elevation > 10 x ULN accompanied by muscle symptoms while on statin therapy and documented resolution of both CK elevation and muscle symptoms upon discontinuation of statin therapy;
AND
d) Symptoms resolved or improved when statin dose was decreased or discontinued
5) Lipid lowering therapy has been stable prior to LDL-C screening for at least 4 weeks if currently on a bile-acid sequestering resin and/or stanol; if subject is on statin or ezetimibe at start of screening, statin or ezetimibe must be discontinued for = 4 weeks before LDL-C screening
6) Fasting triglycerides = 400 mg/dL (4.52 mmol/L) by central laboratory at screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1) History of haemorrahagic stroke
2) Personal or family history of hereditary muscular disorders
3) NYHA III or IV heart failure, or last known left ventricular ejection fraction (LVEF) < 30%
4) Uncontrolled serious cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, in the past 3 months prior to randomization
5) Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
6) Planned cardiac surgery or revascularization
7) Type 1 diabetes, poorly controlled type 2 diabetes (HbA1c > 8.5%), newly diagnosed type 2 diabetes (within 6 months of randomization), or laboratory evidence of diabetes during screening (fasting serum glucose = 126 mg/dL [7.0 mmol/L] or HbA1c = 6.5%) without prior diagnosis of diabetes
8) Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg
9) Subject who has taken in the last 4 weeks prior to LDL C screening red yeast rice, > 200 mg/day niacin, or prescription lipid-regulating drugs (eg, fibrates and derivatives, statins or, ezetimibe) other than bile-acid sequestering resin, or stanols and stanol esters
10) Subject who has taken a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to LDL-C screening, such as: anacetrapib, dalcetrapib or evacetrapib.
11) Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: systemic cyclosporine, systemic steroids (eg, IV, intramuscular [IM], or PO) (Note: hormone replacement therapy is permitted), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane); (Note: vitamin A in a multivitamin preparation is permitted)
12) Uncontrolled hypothyroidism or hyperthyroidism as defined by thyroid stimulating hormone (TSH) < 1.0 time the lower limit of normal or >1.5 times the ULN, respectively, at screening. Potential subjects with TSH < 1.0 time the lower limit of normal due to thyroid replacement therapy is not considered an exclusion
13) Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 at screening
14) Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the ULN as determined by central laboratory analysis at screening
15) Known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator
16) Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months prior to randomization
17) Unreliability as a study participant based on the investigator's (or designee’s) knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis)
18) Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
19) Female subject who has either (1) not used at least 1 highly effective method of contraception for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks af

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified